Randomised clinical trial: the DPP-4 inhibitor, vildagliptin, inhibits gastric accommodation and increases glucagon-like peptide-1 plasma levels in healthy volunteers

Aliment Pharmacol Ther. 2019 Apr;49(8):997-1004. doi: 10.1111/apt.15195. Epub 2019 Mar 3.

Abstract

Background: Dipeptidyl peptidase-4 (DPP-4) inactivates glucagon-like peptide-1 (GLP-1). Whether DPP-4 inhibition affects GLP-1 metabolism and/or food intake in humans remains unknown.

Aims: To evaluate the effect of vildagliptin (DPP-4 inhibitor) on gastric accommodation and ad libitum food intake in healthy volunteers (HVs) METHODS: The effects of acute oral vildagliptin administration (50 mg) were evaluated in two randomised, placebo-controlled, single-blinded trials. Protocol 1 (n = 10, 32.3 ± 3 years, 23.4 ± 0.7 kg/m2 ): 60 min after treatment, a nutrient drink (270 kcal) was infused intragastrically and intragastric pressure (IGP) was measured for 1 h. Protocol 2 (n = 10, 24.3 ± 0.8 years, 22.3 ± 0.9 kg/m2 ): 60 min after treatment, HVs consumed one nutrient drink (300 kcal). Thirty minutes thereafter, HVs ate ad libitum from a free-choice buffet for 30 min. Blood was collected at several time points to measure active GLP-1 plasma levels.

Results: During the first 20 min after nutrient infusion, the drop in IGP was smaller after vildagliptin compared to placebo (treatment-by-time interaction effect: P = 0.008). No differences were seen on epigastric symptom scores. Planned contrast analysis showed that active GLP-1 levels were higher after vildagliptin compared to placebo (P = 0.018) only after nutrient ingestion. Total food intake (316.38 ± 58.89 g vs 399.58 ± 63.02 g, P = 0.359) and total caloric intake (594.77 ± 115.17 kcal vs 742.77 ± 107.10 kcal, P = 0.371) did not differ between treatments.

Conclusions: Vildagliptin inhibits gastric accommodation without affecting epigastric symptom scoring in HVs. Active GLP-1 plasma levels were increased after vildagliptin treatment, but the increase was not sufficient to affect ad libitum food intake. The study was registered at Clincialtrials.gov (NCT 03500900).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dipeptidyl Peptidase 4 / drug effects
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Energy Intake
  • Female
  • Glucagon-Like Peptide 1 / metabolism*
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Male
  • Single-Blind Method
  • Stomach / drug effects
  • Vildagliptin / pharmacology*
  • Young Adult

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Glucagon-Like Peptide 1
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Vildagliptin